Addition of FISH and mutation analyses to cytology analysis significantly increased the level of sensitivity with which we detected malignancy in biliary strictures, with 100% specificity. These techniques can be performed using standard brush samples collected during endoscopic retrograde cholangiopancreatography, with mutations detected in free DNA in supernatant fluid of samples. The tests are complementary and therefore should be used sequentially in the diagnostic evaluation of biliary strictures.

Microarray analysis in transcriptional profiling of PBMCs showed that genes that are uniquely related to molecular and pancreatic function display differential expression in acute pancreatitis. Profiling genes obtained from an easily accessible source during severe pancreatitis may identify surrogate markers for disease severity.

No abstract

Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are two malignancies that carry significant morbidity and mortality. The poor prognoses of these cancers are strongly related to lack of effective screening modalities as well as few therapeutic options. In this review, we highlight novel biomarkers that have the potential to be used as diagnostic, prognostic and predictive markers. The focus of this review is biomarkers that can be evaluated on endoscopically-obtained biopsies or brush specimens in the pre-operative setting. We also provide an overview of novel serum based markers in the early diagnosis of both PDAC and CCA. In pancreatic cancer, the emphasis is placed on prognostic and theranostic markers, whereas in CCA the utility of molecular markers in diagnosis and prognosis are highlighted.

Pancreatitis-associated proteins (PAP) are stress-induced secretory proteins that are implicated in immunoregulation. Previous studies have demonstrated that PAP is up-regulated in acute pancreatitis and that gene knockdown of PAP correlated with worsening severity of pancreatitis, suggesting a protective effect for PAP. In the present study, we investigated the effect of PAP2 in the regulation of macrophage physiology. rPAP2 administration to clonal (NR8383) and primary macrophages were followed by an assessment of cell morphology, inflammatory cytokine expression, and studies of cell-signaling pathways. NR8383 macrophages which were cultured in the presence of PAP2 aggregated and exhibited increased expression of IL-1, IL-6, TNF-α, and IL-10; no significant change was observed in IL-12, IL-15, and IL-18 when compared with controls. Chemical inhibition of the NFκB pathway abolished cytokine production and PAP facilitated nuclear translocation of NF-κB and phosphorylation of IκBα inhibitory protein suggesting that PAP2 signaling involves this pathway. Cytokine responses were dose dependent. Interestingly, similar findings were observed with primary macrophages derived from lung, peritoneum, and blood but not spleen. Furthermore, PAP2 activity was inhibited by the presence of serum, inhibition which was overcome with increased PAP2. Our results demonstrate a new function for PAP2: it stimulates macrophage activity and likely modulates the inflammatory environment of pancreatitis.